Controlled and uncontrolled studies of phosphodiesterase III inhibitors in contemporary cardiovascular medicine

Abstract The phosphodiesterase inhibitors are new inotrope vasodilators that have beneficial hemodynamic effects in patients with congestive heart failure (CHF). The most extensively studied agents are milrinone and enoximone. Both drugs have clearly been shown in numerous studies to improve hemodynamics in patients with CHF when given acutely by either the intravenous or oral route. In long-term studies, milrinone has been shown to have sustained beneficial hemodynamic effects during active treatment. Effects on exercise tolerance have been less clear-cut in several uncontrolled trials, but a recent large-scale randomized trial does show sustained improvement in exercise performance. When milrinone is withdrawn after long-term therapy, some studies show worsened cardiac performance; the exact cause remains ill-defined, but could be due to deterioration of baseline ventricular function or to “rebound.” Both uncontrolled studies and a large recently reported randomized trial show that the hemodynamic response to readministration of milrinone after withdrawal is well-preserved, i.e., no tolerance is observed. Studies of enoximone show that its acute hemodynamic effects are similar to those of milrinone, but its long-term efficacy, using both hemodynamic and exercise end points, is less clear-cut, and no large-scale randomized trials of enoximone therapy have yet been reported. The studies of both these agents performed thus far indicate that the phosphodiesterase inhibitors have considerable promise for both acute and long-term treatment of patients with CHF.